The present invention relates in general to treatments for vascular disease, and more particularly to a method for treating vascular disease by administering a liposomal prostaglandin formulation to a mammal.
Prostaglandins are cyclic, oxygenated fatty acids known to be potent pharmacological agents and to have a potent effect on cell function in many organ systems. Prostaglandin E1 (PGE1), for example, has various pharmacological properties, the most notable being vasodilation, inhibition of platelet aggregation, and stimulation of intestinal and uterine smooth muscle. Major disadvantages of PGE1, however, are its short in-vivo half-life of approximately 30 to 90 seconds, instability, and rapid degradation. When administered intravenously, PGE1 is rapidly metabolized during circulation through the lungs so that its pharmacological effects are significantly diminished by the time it reaches a target site or organ system.
Encapsulation of PGE1 in liposomes solves the problems of instability, short term half-line and rapid degradation experienced with PGE1 in its free form. Liposomes may function as sustained release systems for drugs, and the rate of release may be manipulated. A liposomal formulation of pharmaceutical agents results in a more effective targeted delivery, enabling delivery of the maximum patient tolerated dosage with fewer side effects.
U.S. Pat. No. 4,103,026 describes a method of treating peripheral vascular disease by non-arterial administration of PGE1. The patent discloses that PGE1 in a saline solution is administered intravenously at a dose of 1-10 μg/hr for 10 to 20 minutes once per hour. Even though the PGE1 passes through the patient's lungs before transportation to the patient's extremities, therapeutic effects are reported. Administration of PGE1, however, is limited to hourly injections over an extended period of time. In Example 1 of the patent, the PGE1 dosage disclosed is 2-4 μg/hr administered intravenously for 10 minutes each hour for 3 days.
U.S. Pat. No. 5,925,375 describes the use of multilamellar liposomal prostaglandin formulations for treatment of disorders characterized by cellular activation and adhesion, inflammation and/or toxemia. The liposome disclosed by the patent contains an arachidonic acid metabolite, two or more lipid-containing bilayers and two or more aqueous compartments containing a release-inhibiting citric acid buffer. About 90% of available prostaglandin was associated or partitioned into multilamellar vesicles when a citrate buffer was used to rehydrate dried lipids to form liposomes. The liposomes are about 500 nm in diameter to about 1 micron in diameter. Prostaglandin comprising from about 10−12 g to about 10−3 g of the prostaglandin per kg of the animal's body weight is administered per dose of the composition.